Gene Therapy Breakthrough: One-Time Intrathecal Treatment Significantly Boosts Motor Function in Older SMA Patients, STEER Trial Finds

One-time administration of intrathecal onasemnogene abeparvovec (OA), an adeno-associated vector-based gene therapy, significantly improved motor function compared with a sham control procedure in older patients with spinal muscular atrophy (SMA), according to the results of the phase-3 STEER trial.

The trial met its primary endpoint of change from baseline to 52 weeks in Hammersmith Functional Motor Scale Expanded (HFMSE) score, with OA demonstrating a statistically significant 2.39-point improvement on the HFMSE compared with 0.51 points in the sham group (overall difference, 1.88 points; P=.0074).

Crystal Proud, MD, of Children’s Hospital of the King’s Daughterse, Norfolk, VA, and colleagues presented the results at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.

STEER was a phase-3 trial that enrolled 136 treatment-naïve, sitting and never ambulatory patients aged 2 to younger than 18 years with SMA. The patients were randomly assigned 3:2 to OA or a sham procedure.

In addition to meeting its primary endpoint, the trial showed that all secondary endpoints consistently favored the OA arm; however, the differences between OA and the sham procedure did not meet statistical significance “due to the pre-planned multiple testing procedure.”

The most common serious adverse events were pneumonia and vomiting in patients assigned OA, and pneumonia and lower respiratory tract infection for those who underwent the sham procedure.

In 2019, the Food and Drug Administration approved intravenous onasemnogene abeparvovec for SMA in children less than two years of age.

Reference

Proud C, Wilmshurst JM, Sanmaneechai O, et al. Intrathecal Onasemnogene Abeparvovec for Patients with Spinal Muscular Atrophy: Phase 3, Randomized, Sham-Controlled, Double-Blind STEER Study. LB450. Presented at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference.